Biomedical Engineering Reference
In-Depth Information
Desmosomal Cadherins
In humans, there are seven desmosomal cadherins: three desmocollins (DSC 1-3)
and four desmogleins (DSG 1-4). Both subfamilies have i ve EC domains, although
the i t h domain is less well conserved (Angst
et al.
2001). h e EC1 domains
of DSC and DSG proteins are structurally similar to classical cadherins (e.g., a
conserved tryptophan [W2] and glutamic acid [E89]) and it is likely these proteins
also dimerize via strand swapping (Posy
et al.
2008). Desmosomal cadherins are
believed to form
cis
dimers within a desmosome, then interact with dimers on a
neighboring cell, with heterophilic interactions between DSC and DSG proteins
favored (Angst
et al.
2001).
h e DSC and DSG proteins dif er from classical cadherins and from each
other in their cytoplasmic domains. Both groups contain a membrane proximal
intracellular anchor domain, which corresponds to the JMD in type I cadherins,
and an intracellular cadherin segment (ICS) similar to the CBD in classical
cadherins. h e ICS in DSC and DSG proteins, however, binds predominantly to
γ-catenin and links to the intermediate i lament cytoskeleton (Green and Simpson
2007).
Protocadherins
h e protocadherins are the largest subgroup of the cadherin superfamily, with
at least 70 members (Frank and Kemler 2002). Protocadherins have six or seven
EC domains, a single transmembrane region and divergent cytoplasmic domains.
Members of the protocadherin subfamily do not contain a conserved W2 residue
or a hydrophobic acceptor site in their EC1 domain. Instead, protocadherins have
two cysteine residues and a disuli de loop in the EC1 domain with an RGD motif
(Morishita and Yagi 2007). Interestingly, protocadherins mediate homophilic
and heterophilic adhesion in a
cis
conformation and may be involved in
trans
homophilic adhesion at er forming complexes with other molecules (Frank and
Kemler 2002, Morishita and Yagi 2007). Few intracellular binding partners have
been identii ed for the cytoplasmic domains, but one is the tyrosine kinase Fyn,
which binds to the constant domain of the α-protocadherin family (Frank and
Kemler 2002).
SELECTINS
h e selectins are C-type lectins expressed on the surface of leukocytes, platelets
and activated endothelial cells. Selectins promote the tethering and rolling
of leukocytes and platelets on the vascular endothelium and are important for
lymphocyte homing to secondary lymphoid organs and for the recruitment of
leukocytes to sites of inl ammation (McEver 2002, Cummings and McEver 2009).
h ere are three selectins: L-selectin, expressed on all leukocytes except activated
T-cells; E-selectin, expressed by cytokine-activated endothelial cells; and P-selectin,
